Biology subjects

Cerasa, A.

Publications and source records attributed to Cerasa, A..

3 recordsLinked to original sources

bioRxiv2024

The replication principle revisited: a shared functional organization between pulvinar-cortical and cortico-cortical connectivity and its structural and molecular imaging correlates

The pulvinar, the largest nucleus in the human thalamus, is a complex, highly interconnected structure. Through a dense, organized network of cortical and subcortical areas, it provides adequate cooperation between neural systems, which is crucial for multiple high-order functions such as perception, visuospatial attention, and emotional processing. Such a central role is made possible by a precise internal topographical organization, which is mirrored by anatomical connections as well as by the expression of neurochemical markers. While being traditionally subdivided into sub-nuclei, each characterized by distinct connectional and morphological features, recent studies in both primate and human brains have highlighted that this topographical organization only marginally aligns with the conventional histological subdivision. Instead, it has been delineated in the context of continuous gradients of cortical connections along the dorsoventral and mediolateral axes. While this multi-gradient organization has been extensively documented in primate models, it remains relatively underexplored in the human brain. The present work combines high-quality, multi-modal structural and functional imaging data with a recently published whole-brain, large-scale, positron emission tomography (PET) atlas detailing 19 neurotransmitters and receptors distributed across the human brain. By applying diffusion embedding analysis to tractography, functional connectivity, and receptor coexpression data, we identify and characterize multiple topographically organized gradients of structural connections, functional coactivation, and molecular binding patterns. We demonstrate that such gradients converge on a shared representation along the dorsoventral and mediolateral axes of the human pulvinar. This representation aligns with transitions in both structural and functional connectivity, spanning from lower-level to higher-order cortical regions. Moreover, it is paralleled by gradual changes in the expression of molecular markers associated with key neuromodulator systems, including serotoninergic, noradrenergic, dopaminergic, and opioid systems. Our findings represent a significant step forward in understanding pulvinar anatomy and function, offering an exploratory framework to investigate the role of this structure in both health and disease.

neuroscience↗

bioRxiv2018

Small effect size leads to reproducibility failure in resting-state fMRI studies

Thousands of papers using resting-state functional magnetic resonance imaging (RS-fMRI) have been published on brain disorders. Results in each paper may have survived correction for multiple comparison. However, since there have been no robust results from large scale meta-analysis, we do not know how many of published results are truly positives. The present meta-analytic work included 60 original studies, with 57 studies (4 datasets, 2266 participants) that used a between-group design and 3 studies (1 dataset, 107 participants) that employed a within-group design. To evaluate the effect size of brain disorders, a very large neuroimaging dataset ranging from neurological to psychiatric isorders together with healthy individuals have been analyzed. Parkinsons disease off levodopa (PD-off) included 687 participants from 15 studies. PD on levodopa (PD-on) included 261 participants from 9 studies. Autism spectrum disorder (ASD) included 958 participants from 27 studies. The meta-analyses of a metric named amplitude of low frequency fluctuation (ALFF) showed that the effect size (Hedges g) was 0.19 - 0.39 for the 4 datasets using between-group design and 0.46 for the dataset using within-group design. The effect size of PD-off, PD-on and ASD were 0.23, 0.39, and 0.19, respectively. Using the meta-analysis results as the robust results, the between-group design results of each study showed high false negative rates (median 99%), high false discovery rates (median 86%), and low accuracy (median 1%), regardless of whether stringent or liberal multiple comparison correction was used. The findings were similar for 4 RS-fMRI metrics including ALFF, regional homogeneity, and degree centrality, as well as for another widely used RS-fMRI metric namely seed-based functional connectivity. These observations suggest that multiple comparison correction does not control for false discoveries across multiple studies when the effect sizes are relatively small. Meta-analysis on un-thresholded t-maps is critical for the recovery of ground truth. We recommend that to achieve high reproducibility through meta-analysis, the neuroimaging research field should share raw data or, at minimum, provide un-thresholded statistical images.

neuroscience↗

bioRxiv2016

Tractography-based connectomes are dominated by false-positive connections

Fiber tractography based on non-invasive diffusion imaging is at the heart of connectivity studies of the human brain. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain dataset with ground truth white matter tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. While most state-of-the-art algorithms reconstructed 90% of ground truth bundles to at least some extent, on average they produced four times more invalid than valid bundles. About half of the invalid bundles occurred systematically in the majority of submissions. Our results demonstrate fundamental ambiguities inherent to tract reconstruction methods based on diffusion orientation information, with critical consequences for the approach of diffusion tractography in particular and human connectivity studies in general.

neuroscience↗